Daniel E Furst1. 1. Rheumatology Division, Geffen School of Medicine, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90025-1670, USA. defurst@mednet.ucla.edu
Abstract
BACKGROUND: Interleukin-1 (IL-1) plays an important role in the pathophysiology and progression of rheumatoid arthritis (RA) by contributing to destruction of cartilage, bone, and periarticular tissues. Inhibiting IL-1 synthesis or activity with the use of recombinant human IL-1 receptor antagonist (anakinra) may prove to be an effective approach to the treatment of RA. OBJECTIVE: The purpose of this article is to review the effects of anakinra in the treatment of RA. METHODS: A MEDLINE search from 1982 to 2003 was used to identify animal studies and randomized clinical trials of anakinra and other therapies that target IL-1. RESULTS: Clinical trials of anakinra have shown that it reduces the signs and symptoms of active disease and slows the rate of radiographic destruction in adults with RA. With anakinra 150 mg/d, 43% of patients achieved an American College of Rheumatology (ACR) 20% response, compared with 27% with placebo (P = 0.014). The ACR20 score indicates at least 20% improvement in the ACR composite score, which includes assessment of tender and swollen joint count, and other clinical end points such as pain and disability assessment. Patients treated with anakinra also experienced a 59% reduction in new bony erosion compared with controls (P < 0.001) and a 65% reduction in joint space narrowing as measured by the modified Sharp score (P = 0.020). Injection-site reactions were the most commonly reported adverse event, occurring in 50%, 73%, and 81% of patients receiving anakinra 30, 75, and 150 mg/d, respectively, compared with 25% of patients receiving placebo. Few serious adverse events were reported, and they typically occurred in patients receiving the highest daily dosage. CONCLUSIONS: IL-1 is an important cytokine in promoting the damage associated with RA. Anakinra is mildly to moderately effective and well tolerated in patients with active RA when used as monotherapy or in combination with methotrexate.
BACKGROUND:Interleukin-1 (IL-1) plays an important role in the pathophysiology and progression of rheumatoid arthritis (RA) by contributing to destruction of cartilage, bone, and periarticular tissues. Inhibiting IL-1 synthesis or activity with the use of recombinant humanIL-1 receptor antagonist (anakinra) may prove to be an effective approach to the treatment of RA. OBJECTIVE: The purpose of this article is to review the effects of anakinra in the treatment of RA. METHODS: A MEDLINE search from 1982 to 2003 was used to identify animal studies and randomized clinical trials of anakinra and other therapies that target IL-1. RESULTS: Clinical trials of anakinra have shown that it reduces the signs and symptoms of active disease and slows the rate of radiographic destruction in adults with RA. With anakinra 150 mg/d, 43% of patients achieved an American College of Rheumatology (ACR) 20% response, compared with 27% with placebo (P = 0.014). The ACR20 score indicates at least 20% improvement in the ACR composite score, which includes assessment of tender and swollen joint count, and other clinical end points such as pain and disability assessment. Patients treated with anakinra also experienced a 59% reduction in new bony erosion compared with controls (P < 0.001) and a 65% reduction in joint space narrowing as measured by the modified Sharp score (P = 0.020). Injection-site reactions were the most commonly reported adverse event, occurring in 50%, 73%, and 81% of patients receiving anakinra 30, 75, and 150 mg/d, respectively, compared with 25% of patients receiving placebo. Few serious adverse events were reported, and they typically occurred in patients receiving the highest daily dosage. CONCLUSIONS:IL-1 is an important cytokine in promoting the damage associated with RA. Anakinra is mildly to moderately effective and well tolerated in patients with active RA when used as monotherapy or in combination with methotrexate.
Authors: Catherine E Vrentas; Robert G Schaut; Paola M Boggiatto; Steven C Olsen; Fayyaz S Sutterwala; Mahtab Moayeri Journal: Vet Immunol Immunopathol Date: 2018-05-21 Impact factor: 2.046
Authors: Benjamin W Van Tassell; Michael J Lipinski; Darryn Appleton; Charlotte S Roberts; Michael C Kontos; Nayef Abouzaki; Ryan Melchior; George Mueller; James Garnett; Justin Canada; Salvatore Carbone; Leo F Buckley; George Wohlford; Dinesh Kadariya; Cory R Trankle; Claudia Oddi Erdle; Robin Sculthorpe; Laura Puckett; Christine DeWilde; Keyur Shah; Dominick J Angiolillo; George Vetrovec; Giuseppe Biondi-Zoccai; Ross Arena; Antonio Abbate Journal: Clin Cardiol Date: 2018-08-17 Impact factor: 2.882
Authors: Antonio Abbate; Benjamin Wallace Van Tassell; Giuseppe Biondi-Zoccai; Michael Christopher Kontos; John Dallas Grizzard; Debra Whittaker Spillman; Claudia Oddi; Charlotte Susan Roberts; Ryan David Melchior; George Herman Mueller; Nayef Antar Abouzaki; Lenore Rosemary Rengel; Amit Varma; Michael Lucas Gambill; Raquel Appa Falcao; Norbert Felix Voelkel; Charles Anthony Dinarello; George Wayne Vetrovec Journal: Am J Cardiol Date: 2013-02-27 Impact factor: 2.778